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European Journal of Medicinal Chemistry Sep 2019Curcumin is a pharmacologically active polyphenol derived from the popular spice element-Turmeric. The therapeutic activity of curcumin has been extensively investigated... (Review)
Review
Curcumin is a pharmacologically active polyphenol derived from the popular spice element-Turmeric. The therapeutic activity of curcumin has been extensively investigated over the last few decades and reports suggest the role of curcumin in a large number of biological activities, particularly its prominent anticancer activity. Curcumin, being a pleiotropic molecule, is a regulator of multiple molecular targets which play crucial roles in various cell signaling pathways. It is known to suppress transformation, inhibit proliferation as well as induce apoptosis. However, despite all these benefits, the efficacy of curcumin remains limited due to its poor bioavailability, poor absorption within the systemic circulation and rapid elimination from the body. To overcome these limiting factors, researchers all around the world are working towards designing a synthetic and superior curcuminoid by making suitable structural modifications to the parent skeleton. These curcuminoids, mainly analogues and derivatives, will not only improve the physicochemical properties but also enhance the efficacy simultaneously. The present review will provide a comprehensive account of the analogues and derivatives of curcumin that have been reported since 2014 which have indicated a better anticancer activity than curcumin.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Curcumin; Humans; Molecular Structure
PubMed: 31129455
DOI: 10.1016/j.ejmech.2019.04.058 -
Current Opinion in Pharmacology Dec 2018Dumping syndrome is a common and debilitating complication of upper gastrointestinal surgery. Accelerated gastric emptying and dysregulated secretion of gastrointestinal... (Review)
Review
Dumping syndrome is a common and debilitating complication of upper gastrointestinal surgery. Accelerated gastric emptying and dysregulated secretion of gastrointestinal (GI) hormones are involved in its pathophysiology. Pasireotide, a novel somatostatin analogue, improved dumping in a phase-2 study. Preliminary data suggest that the glucagon-like peptide-1 (GLP-1) analogue liraglutide can also improve dumping. Short bowel syndrome is the most common cause of intestinal failure and involves not only a loss of mucosal absorptive area but also hypersecretion and accelerated transit. GLP-2 is the best studied hormone involved in intestinal adaptation. An increasing body of evidence demonstrates that the GLP-2 analogue teduglutide reduces parenteral support needs. New GLP-2 analogues and analogues of other GI hormones such as liraglutide are being investigated as promising treatments in short bowel syndrome.
Topics: Animals; Dumping Syndrome; Gastrointestinal Agents; Gastrointestinal Motility; Gastrointestinal Tract; Humans; Intestinal Absorption; Ligands; Liraglutide; Peptides; Receptors, Gastrointestinal Hormone; Short Bowel Syndrome; Signal Transduction; Somatostatin; Treatment Outcome
PubMed: 30273889
DOI: 10.1016/j.coph.2018.09.005 -
Khirurgiia 2020Prospective randomized investigation of the efficiency of somatostatin analogues and glucocorticoids in pancreatic fistula prevention after pancreatoduodenectomy by... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Prospective randomized investigation of the efficiency of somatostatin analogues and glucocorticoids in pancreatic fistula prevention after pancreatoduodenectomy by using.
MATERIAL AND METHODS
In period from December 2018 till March 2020 78 patients underwent pancreatoduodenectomy for pancreatobilliary tumors in department of abdominal surgery of National Medical Research Center of Surgery named after A.V. Vishnevsky. Intraoperative frozen section investigation of pancreatic functioning acinar structures (FAS) was held for all patients. 38 patients had more than 40% of FAC and were related with high risk of pancreatic fistula (PF), while 40 patients with less than 40% FAC were included in low risk of PF group. In both groups patients were randomized to main and control subgroups. In main subgroup of high risk group patients combination of somatostatin analogues and glucocorticoids was used, while in control subgroup patients received only somatostatin analogue. In low risk of PF group patients of main subgroup preventively got somatostatin analogue, while control group patients had no specific prophylaxis of PF. To assess the effect of drug prophylaxis on the development of pancreatic fistula we used logistic regression models with the inclusion of the drug use factor as an independent variable.
RESULTS
25 patients were included in main subgroup of high risk group. Clinically relevant pancreatic fistula (CRPF) developed in 14 (56%) cases. From 13 patients of control subgroup CRPF developed in 5 (38%) cases. In main subgroup of low risk group 18 patients were included and 3 (16%) of them had CRPF. In control subgroup were 22 patients and there were no cases of CRPF.
CONCLUSION
In our series combination of somatostatin analogue and glucocorticoid didn't show efficiency in prevention of CRPF in high risk patients, although difference between subgroups wasn't statistically significant (=0.34). In low risk group patients prophylactic use of somatostatin analogue also didn't show decline of CRPF incidence and the difference between subgroups also wasn't statistically significant (=0.46).
Topics: Biliary Tract Neoplasms; Gastrointestinal Agents; Glucocorticoids; Humans; Pancreas; Pancreatic Fistula; Pancreatic Neoplasms; Pancreaticoduodenectomy; Prospective Studies; Somatostatin
PubMed: 33210509
DOI: 10.17116/hirurgia202011161 -
Current Molecular Pharmacology 2018New psychoactive substances (NPS), often referred to as "legal highs" or "designer drugs", are derivatives and analogues of existing psychoactive drugs that are... (Review)
Review
BACKGROUND
New psychoactive substances (NPS), often referred to as "legal highs" or "designer drugs", are derivatives and analogues of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse.
OBJECTIVE
This systematic review aims to gather the state of the art regarding chemical, molecular pharmacology and toxicological information of opioid class of NPS.
METHODS
Chemical, pharmacological, toxicological and clinical effects of opioid class of NPS were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period.
RESULTS
Within this class, fentanyl analogues are among the most frequently abused and pose several clinical concerns and therefore will be thoroughly discussed. Other opioid sub-categories of NPS frequently misused include AH-7921, MT-45, U-47700, U-50488, desomorphine, mitragynine, tramadol, tapentadol, salvinorin A and its analogue herkinorin.
CONCLUSION
Due to inefficient monitoring techniques, as well as limited knowledge regarding the acute and long-term effects of opioids NPS, further clinical and forensic toxicological studies are required.
Topics: Analgesics, Opioid; Fentanyl; Humans; Psychotropic Drugs
PubMed: 28676005
DOI: 10.2174/1874467210666170704110146 -
Biomedicine & Pharmacotherapy =... May 2024The mast cell receptor Mrgprb2, a mouse orthologue of human Mrgprx2, is known as an inflammatory receptor and its elevated expression is associated with various diseases...
The mast cell receptor Mrgprb2, a mouse orthologue of human Mrgprx2, is known as an inflammatory receptor and its elevated expression is associated with various diseases such as ulcerative colitis. We aimed to elucidate the role of Mrgprb2/x2 and the effect of its ligands on a chemically induced murine colitis model. We showed that in Mrgprb2 mice, there is a differential regulation of cytokine releases in the blood plasma and severe colonic damages after DSS treatment. Unexpectedly, we demonstrated that known Mrgprb2/x2 agonists (peptide P17, P17 analogues and CST-14) and antagonist (GE1111) similarly increased the survival rate of WT mice subjected to 4% DSS-induced colitis, ameliorated the colonic damages of 2.5% DSS-induced colitis, restored major protein mRNA expression involved in colon integrity, reduced CD68 and F4/80 immune cell infiltration and restored cytokine levels. Collectively, our findings highlight the eminent role of Mrpgrb2/x2 in conferring a beneficial effect in the colitis model, and this significance is demonstrated by the heightened severity of colitis with altered cytokine releases and inflammatory immune cell infiltration observed in the Mrgprb2 knockout mice. Elevated expression of Mrgprb2 in WT colitis murine models may represent the organism's adaptive protective mechanism since Mrgprb2 knockout results in severe colitis. On the other hand, both agonist and antagonist of Mrgprb2 analogously mitigated the severity of colitis in DSS-induced colitis model by altering Mrgprb2 expression, immune cell infiltration and inflammatory cytokine releases.
Topics: Animals; Dextran Sulfate; Mice, Knockout; Colitis; Mice, Inbred C57BL; Mice; Cytokines; Receptors, G-Protein-Coupled; Colon; Male; Disease Models, Animal; Receptors, Neuropeptide
PubMed: 38547764
DOI: 10.1016/j.biopha.2024.116471 -
Trends in Cognitive Sciences Jun 2022Neural dynamics are shaped and constrained by the projections of a small nucleus in the pons: the noradrenergic locus coeruleus (LC). Much like a bow to the brain's... (Review)
Review
Neural dynamics are shaped and constrained by the projections of a small nucleus in the pons: the noradrenergic locus coeruleus (LC). Much like a bow to the brain's violin, activity in the LC lacks content specificity, but instead dynamically shapes the excitability and receptivity of neurons across the brain. In this review, we explain how the style of the bowing technique, which is analogous to different firing modes in the LC, affects distinct activity patterns in the rest of the brain. Through this analogical lens, we provide intuitive insights into how the complex activity of the LC acts to coordinate adaptive neural dynamics.
Topics: Humans; Locus Coeruleus; Neurons
PubMed: 35469726
DOI: 10.1016/j.tics.2022.03.006 -
Medicinal Chemistry Research : An... 2022During the last years, the progression to control malaria disease seems to be slowed and WHO (World Health Organization) reported a modeling analysis with the prediction...
During the last years, the progression to control malaria disease seems to be slowed and WHO (World Health Organization) reported a modeling analysis with the prediction of the increase in malaria morbidity and mortality in sub-Saharan Africa during the COVID-19 pandemic. A rapid way to the discovery of new drugs could be carried out by performing investigations to identify drugs based on repurposing of "old" drugs. The 5-nitrothiazole drug, Nitazoxanide was shown to be active against intestinal protozoa, human helminths, anaerobic bacteria, viruses, etc. In this work, Nitazoxanide and analogs were prepared using two methodologies and evaluated against 3D7. A bithiazole analog, showed attractive inhibitory activity with an EC value of 5.9 μM, low propensity to show toxic effect against HepG2 cells at 25 μM, and no cross-resistance with standard antimalarials.
PubMed: 35106047
DOI: 10.1007/s00044-021-02843-1 -
Diabetes, Obesity & Metabolism Aug 2016Biosimilars are regulated differently from small-molecule generic, chemically derived medicines. The complexity of biological products means that small changes in... (Review)
Review
Biosimilars are regulated differently from small-molecule generic, chemically derived medicines. The complexity of biological products means that small changes in manufacturing or formulation may result in changes in efficacy and safety of the final product. In the face of this complexity, the regulatory landscape for biosimilars continues to evolve, and global harmonization regarding requirements is currently lacking. It is essential that clinicians and patients are reassured that biosimilars are equally safe and effective as their reference product, and this is particularly important when interchangeability, defined as 'changing one medicine for another one which is expected to achieve the same clinical effect in a given clinical setting in any one patient', is considered. Although the automatic substitution (i.e. substitution without input from the prescribing healthcare provider) of biosimilars for reference products is currently not permitted by the majority of countries, this may change in the future. In order to demonstrate interchangeability between reference products and a biosimilar, more stringent and specific studies of the safety and efficacy of biosimilars are likely to be needed; however, guidance on the design of and the need for any such studies is currently limited. The present article provides an overview of the current regulatory framework around the demonstration of interchangeability with biosimilars, with a specific focus on biosimilar insulin analogues, and details experiences with other biosimilar products. In addition, designs for studies to evaluate interchangeability with a biosimilar insulin analogue product are proposed and a discussion about the implications of interchangeability in clinical practice is included.
Topics: Biosimilar Pharmaceuticals; Chemistry, Pharmaceutical; Drug Substitution; Drug and Narcotic Control; Drugs, Generic; Humans; Hypoglycemic Agents; Insulin
PubMed: 27097592
DOI: 10.1111/dom.12676 -
PloS One 2023This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (TR) (PubChem CID:90659753)- identified to be a novel secondary...
This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (TR) (PubChem CID:90659753)- identified to be a novel secondary metabolite derived from Streptomyces sp (R2). TR was tested in-vitro against drug resistant TB clinical isolates (n = 49). 94% of DR-TB strains (n = 49) were inhibited by TR at 10μg ml-1. In-vivo safety and efficacy studies showed that 0.005mg kg-1 of TR is toxic to mice, rats and guinea pigs, while 0.001mg kg-1 is safe, infection load did not reduce. TR is a potent DNA intercalator and also targets RecA and methionine aminopeptidases of Mycobacterium. Analogue 47 of TR was designed using in-silico based molecule detoxification approaches and SAR analysis. The multiple targeting nature of the TR brightens the chances of the analogues of TR to be a potent TB therapeutic molecule even though the parental compound is toxic. Analog 47 of TR is proposed to have non-DNA intercalating property and lesser in-vivo toxicity with high functional potency. This study attempts to develop a novel anti-TB molecule from microbial sources. Though the parental compound is toxic, its analogs are designed to be safe through in-silico approaches. However, further laboratory validations on this claim need to be carried out before labelling it as a promising anti-TB molecule.
Topics: Animals; Guinea Pigs; Mice; Rats; Mycobacterium tuberculosis; Intercalating Agents; Laboratories; Product Labeling; Research Design; Streptomyces
PubMed: 36867599
DOI: 10.1371/journal.pone.0282454 -
Neural Computation Mar 2022Quantum dynamical systems are capable of powerful computation but are hard to emulate on digital computers. We show that four novel analog circuit parts can emulate the...
Quantum dynamical systems are capable of powerful computation but are hard to emulate on digital computers. We show that four novel analog circuit parts can emulate the phase-coherent unitary dynamics of such systems. These four parts are: a Planck capacitance analogous to a neuronal membrane capacitance; a quantum admittance element, together with the Planck capacitance, analogous to a neuronal quadrature oscillator; a quantum transadmittance element analogous to a complex neuronal synapse; and a quantum transadmittance mixer element analogous to a complex neuronal synapse with resonant modulation. These parts may be emulated classically, with paired real-value voltages on paired Planck capacitances corresponding to the real and imaginary portions of a probability amplitude; and appropriate paired real-value currents onto these Planck capacitances corresponding to diagonal (admittance), off-diagonal (transadmittance), or controlled off-diagonal (transadmittance mixer) Hamiltonian energy terms. The superposition of 2n simultaneously phase-coherent and symmetric probability-voltage amplitudes with O(n) of these parts, in a tensor-product architecture enables analog emulation of the quantum Fourier transform (QFT). Implementation of our circuits on an analog integrated circuit in a 0.18 μm process yield experimental results consistent with mathematical theory and computer simulations for emulations of NMR, Josephson junction, and QFT dynamics. Our results suggest that linear oscillatory neuronal networks with pairs of complex subthreshold/nonspiking sine and cosine neurons that are coupled together via complex synapses to other such complex neurons can architect quantum-inspired computation with classical analog circuits. Thus, an analog-circuit mapping between quantum and neural computation, both of which exploit analog computation for powerful operation, can enable future synergies between these fields.
Topics: Computer Simulation; Computers; Neurons; Synapses
PubMed: 35231932
DOI: 10.1162/neco_a_01481